Synthesis and Evaluation of a Library of Alternating Amphipathic Copolymers to Solubilize and Study Membrane Proteins

25 November 2021, Version 2
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Amphipathic copolymers such as poly(styrene-maleic acid) (SMA) are promising tools for the facile extraction of membrane proteins (MPs) into native nanodiscs. Here, we designed and synthesized a library of well-defined alternating copolymers of SMA analogues in order to elucidate polymer properties that are important for MP solubilization and stability. MP extraction efficiency was determined using KcsA from E.coli membranes and general solubilization efficiency was investigated via turbidimetry experiments on membranes of E.coli, yeast mitochondria and synthetic lipids. Remarkably, halogenation of SMA copolymers dramatically improved solubilization efficiency in all systems, while substituents on the copolymer backbone improved resistance to Ca2+. Relevant polymer properties were found to include hydrophobic balance, size and positioning of substituents, rigidity and electronic effects. The library thus contributes to the rational design of copolymers for the study of MPs.

Keywords

Amphipathic copolymers
copolymer design
membrane proteins
native nanodiscs
polymers

Supplementary materials

Title
Description
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Title
SI - SMA Analogues
Description
Supporting Information - Synthesis and Evaluation of a Library of Alternating Amphipathic Copolymers to Solubilize and Study Membrane Proteins
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